Discarding Functional Residues from the Substitution Table Improves Predictions of Active Sites within Three-Dimensional Structures
Figure 3
Predicting Four Categories of Functional Residues by CRESCENDO.
Four case-studies of predicting functional residues are shown; (A) active-sites, (B) PPI (protein–protein interaction), (C) PNI (protein–nucleic acid interaction, (D) PLI (protein–ligand interaction). SCOP domains d1evua4 [23], d1i7kb_ [24], d1k8wa5 [33] and d1ed9a_ [34] were used for A, B, C, and D, respectively. True positives (TP) are coloured in pink, false negatives (FN, missing residues) in orange and false positives (FP) in green. TP and FN are shown as sticks (bold-frame). (A) Cysteine protease. CRESCENDO predicted 27 residues as functional residues. All three (CYS-314, HIS-373 and ASP-396) catalytic residues were correctly identified. ALL-B type ESST (see Table 2) was used in this figure. FP (green) are clustered around the three real active sites (pink). (B) Ubiquitin conjugating (UBC) enzyme. 12 residues were predicted by CRESCENDO using ALL-A ESST. Five (coloured in pink) were correctly identified among 14 residues annotated as PPI residues. Interacting partner (A chain of 1i7k) is placed at the bottom and coloured in gray. The solvent accessible surface areas (SASA) for five TP are as follow; ARG-34 (35.64), PRO-90 (4.12), SER-123 (4.74), ALA-124 (0.55), LEU-125 (72.39). SASA for 9 FN are as follow; PRO-30 (77.26), VAL-31 (24.02), SER-87 (110.40), GLY-88 (16.05), TYR-89 (0.01), TYR-91 (58.29), GLU-120 (108.68), LYS-121 (113.96), TRP-122 (7.20). The SASA is from InterPare [18]. (C) Pseudouridine synthase. BIPA (S. Lee, unpublished) annotates 43 residues as PNI. 14 residues were TP (coloured in pink) among 20 residues predicted by CRESCENDO. ALL-D was used as ESST. DNA is coloured in blue. (D) Alkaline phosphatase. UniProt annotates 9 residues as metal-binding (METAL), which were all correctly identified by CRESCENDO among 30 predicted residues. ALL-B was used as ESST. ZN (zinc) and MG (magnesium) are coloured in cyan and blue, respectively.